Process for the preparation of an oxirane, azirdine or cyclopropane

ABSTRACT

A process for the preparation of an oxirane, aziridine or cyclopropane of formula (I) wherein, X is oxygen, NR 4  or CHR 5  ; R 1  is hydrogen, alkyl, aryl, heteroaromatic, heterocyclic or cycloalkyl; R 2  is hydrogen, alkyl, aryl, heteroaromatic, CO 2  R 8 , CHR 14  NHR 13 , heterocyclic or cycloalkyl; or R 1  and R 2  join together to form a cycloalkyl ring; R 3  is hydrogen, alkyl, aryl, heteroaromatic, CO 2  R 8 , R 8   3  Sn, CONR 8  R 9  or trimethylsilyl; R 4  and R 5  are, independently, alkyl, cycloalkyl, aryl, heteroaromatic, SO 2  R 8 , SO 3  R 8 , COR 8 , CO 2  R 8 , CONR 8  R 9  or CN, or R 4  can also be P(O)(aryl) 2  ; R 8  and R 9  are independently alkyl, aryl or arylalkyl; R 13  and R 14  are independently hydrogen, alkyl or aryl; the process comprising reacting a mixture of a compound of formula (II), wherein R 1 , R 2  and X are as defined above, and a sulphide of formula SR 6  R 7 , wherein R 6  and R 7  are independently alkyl, aryl or heteroaomatic, or R 6  and R 7  join together to form a cycloalkyl ring which optionally includes an additional heteroatom, with either (i) a metallocarbon obtainable by reacting an alkylmetal with a methane derivative of formula CHR 3  X&#39;X&#34;, wherein R 3  is as defined above, and X&#39; and X&#34; are independently, a leaving group, or (ii) a metallocarbon obtainable by reacting a compound of formula (III), (wherein R 3  may not be hydrogen) with a suitable organometallic or inorganic reagent.

This application is a 371 of PCT/GB94/02280 filed Oct. 19, 1994.

The present invention relates to a process for the preparation ofoxiranes from aldehydes or ketones, of aziridines from imines, or ofcyclopropanes from alkenes.

It is known to generate ylides from diazo compounds in the presence ofrhodium (II) acetate (M. P. Doyle et al J. Org. Chem. (1981) 465094-5102). The use of sulphur ylides to prepare oxiranes from carbonylcompounds is well known (see, for example, B. M. Trost and L. S. Melvin"Sulphur Ylides" Academic Press, 1975). Known methods require that thereaction is carried out under basic conditions. Thus, forming oxiranesof carbonyl substrates which also contain base sensitive groups is notstraightforward. Also, known methods require stoichiometric amounts ofsulphide and base.

According to the present invention there is provided a process for thepreparation of an oxirane, aziridine or cyclopropane of formula (I),wherein, X is oxygen, NR⁴ or CHR⁵ ; R¹ is hydrogen, alkyl, aryl,heteroaromatic, heterocyclic, NHR¹³ or cycloalkyl; R² is hydrogen,alkyl, aryl, heteroaromatic, CO₂ R⁸, CHR¹⁴ NHR¹³, heterocyclic orcycloalkyl; or R¹ and R² join together to form a cycloalkyl ring; R³ ishydrogen, alkyl, aryl, heteroaromatic, CO₂ R⁸, R⁸ ₃ Sn, CONR⁸ R⁹ ortrimethylsilyl; R⁴ and R⁵ are, independently, alkyl, cycloalkyl, aryl,heteroaromatic, SO₂ R⁸, SO₃ R⁸, COR⁸, CO₂ R⁸, CONR⁸ R⁹ or CN, or R⁴ canalso be P(O)(aryl)₂ ; R⁸ and R⁹ are independently alkyl, aryl orarylalkyl; R¹³ and R¹⁴ are independently hydrogen, alkyl or aryl; theprocess comprising reacting a mixture of a compound of formula (II),wherein R¹, R² and X are as defined above, and a sulphide of formula SR⁶R⁷ wherein R⁶ and R⁷ are independently alkyl, aryl or heteroaromatic, orR⁶ and R⁷ join together to form a cycloalkyl ring which optionallyincludes an additional heteroatom, with either (i) a metallocarbonobtainable by reacting an alkylmetal with a methane derivative offormula CHR³ X'X", wherein R³ is as defined above, and X' and X" areindependently, a leaving group, or (ii) a metallocarbon obtainable byreacting a compound of formula (III) (wherein R³ may not be hydrogen)with a suitable organometallic or inorganic reagent.

When the compound of formula (II) is an alkene (that is when X in thecompound of formula (II) is CHR⁵) it is an electron deficient alkene.

When a compound of formula (II) (wherein X is O and neither R¹ nor R² ishydrogen (ie it is a ketone)) is used in the process of the presentinvention to prepare a required oxirane of formula (I) (wherein X is O),the reactivity of the compound of formula (II) should be balancedagainst the nucleophilicity of the product obtained by reacting themetallocarbon of (i) or (ii) with a sulphide of formula SR⁶ R⁷.

It is preferred that the process of the present invention is carried outin a solvent. Suitable solvents include chlorinated solvents (such asCH₂ Cl₂ or CHCl₃), aromatic solvents (such as benzene, toluene and o-,m- or p-xylene), aliphatic alcohols (such as methanol, ethanol ortert-butanol), chain or cyclic ethers (such as diethyl ether, tert-butylmethyl ether, di-iso-propyl ether, glymes (for example monoglyme,diglyme or triglyme) or tetrahydrofuran), aliphatic or alicyclichydrocarbons (such as n-hexane or cyclohexane), N,N-dimethylformamide,acetonitrile or N-methylpyrrolidone. The process may be carried out in amixture of these solvents, or different reagents may be added indifferent solvents.

It is preferred that the process of the present invention is carried outat a temperature in the range -30°-100° C., especially in the range0°-50° C., such as at ambient or room temperature.

The compounds of formula (I) have one, two or three chiral ring-carbonatoms and the process of the present invention is capable of forming allstructural isomers of the compounds of formula (I). Chiral values of R¹,R², R³, R⁴ or R⁵ can affect the stereochemical nature of the compound offormula (I) produced by the process of the present invention.

The term alkyl whenever it is used refers to straight or branched alkylchains preferably containing from 1 to 10, especially from 1 to 6, forexample from 1 to 4, carbon atoms. Alkyl is, for example, methyl, ethyl,n-propyl, n-butyl or tert-butyl.

Halogen is fluorine, chlorine, bromine or iodine.

Alkoxy and haloalkoxy groups are straight or branched chains, preferablycontaining from 1 to 4 carbon atoms.

Haloalkoxy and haloalkyl groups do not have a halogen that issusceptible to nucleophilic substitution. Thus, a carbon atom of ahaloalkyl or haloalkoxy group must not carry a halogen atom and ahydrogen atom.

Aryl includes naphthyl but is preferably phenyl.

Heteroaromatic includes 5- and 6-membered aromatic rings containing one,two, three or four heteroatoms selected from the list comprising oxygen,sulphur and nitrogen and can be fused to benzenoid ring systems.Examples of heteroaromatic rings are pyridyl, pyrimidyl, pyridazinyl,pyrazinyl, triazinyl (1,2,3-, 1,2,4- and 1,3,5-), furyl, thienyl,pyrrolyl, pyrazolyl, imidazolyl, triazolyl (1,2,3- and 1,2,4-),tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, quinolinyl,isoquinolinyl, cinnolinyl, quinazolinyl, quinoxalinyl, indolinyl,isoindolinyl, benzofuranyl, benzothienyl, benzimidazolyl, benzoxazole,benzthiazole, oxadiazole and thiadiazole.

Heterocyclic relates to non-aromatic rings and includes include 5- and6-membered rings containing one, two or three heteroatoms selected fromthe group comprising oxygen, sulphur and nitrogen. Examples arepiperidine, pyrrolidine, azetidine, morpholine, tetrahydrofuran,tetrahydrothiophene, pyrroline, piperazine, isoxazoline and oxazoline.Heterocyclic rings are optionally substituted with one or more alkylgroups.

The ring formed when R⁶ and R⁷ join preferably contains from 1 to 12(for example from 2 to 10, especially from 2 to 6) carbon atoms andoptionally includes an additional heteroatom (preferably a nitrogen,oxygen or sulphur atom). The ring so formed can be substituted by one ormore alkyl groups or can have one or two aryl rings fused to it (see,for example, (G)). Two ring carbons may be linked together through acarbon chain (optionally containing from 1 to 6 (preferably 1, 2, 3 or4) carbon atoms) or through a chain comprising one or more oxygen andone or more carbon atoms (for example to form a methylenedioxy group).The further ring formed may be substituted by C₁₋₄ alkyl. The sulphideof formula SR⁶ R⁷ is, for example, dimethylsulphide, diethylsulphide,(4-methoxyphenyl)methylsulphide or a sulphide of formula (A), (B), (C),(C'), (D), (E) or (F) wherein R' and R" are, independently, hydrogen,alkyl, aryl or arylalkyl.

Suitable organometallic or inorganic reagents preferably compriserhodium or ruthenium. Suitable reagents include Rh₂ (OCOR*)₄, Rh₂ (NR¹⁵COR*)₄ or Ru₂ (OCOR*)₄ (wherein R¹⁵ is hydrogen, alkyl (especiallymethyl) or arylalkyl (such as benzyl; and R* is hydrogen, alkyl(preferably methyl), C₁₋₄ perfluoroalkyl (such as trifluoromethyl,2,2,2-trifluoroethyl or pentafluoroethyl), aryl, (CHOH)alkyl or(CHOH)aryl), Rh₂ (OCOCH₃)₄, Rh₂ (OCOCF₃)₄, Rh₂ (NHCOCH₃)₄, Rh₂(NHCOCF₃)₄, RuCl₂ (P(C₆ H₅)₃)₂, RuCl(H₂ C₂ B₉ H₁₀)(P(C₆ H₅)₃)₂ or Rh₆(CO)₁₆. Alternatively, the rhodium or ruthenium reagent can comprise thegroup (H), wherein R¹⁶ is alkyl, aryl or arylalkyl; and p is 2 or 3.

Alternatively, a suitable organometallic or inorganic reagent cancomprise copper, nickel or palladium. Examples of suitable reagentsinclude CuBr, CuCl, CuOSO₂ CF₃, CuBr₂, CuCl₂, CuSO₄, ⁻Cu(acetylacetate)₂, Cu(CH₃ CN)₄ !BF₄, Pd(OCOCH₃)₂, Pd(CH₃ CN)₂ Cl₂ orPd(C₆ H₅ CN)₂ Cl₂.

It is believed that a metallocarbene of formula M═CHR³ (wherein M is,for example, rhodium, ruthenium, copper, nickel or palladium, and R³ isas defined above but is not hydrogen) is produced by the reaction of acompound of formula (III) (wherein R³ is not hydrogen) with a suitableorganometallic or inorganic reagent.

A metallocarbon obtainable by reacting an alkylmetal (such as a dialkylzinc or a trialkyl aluminium compound) with a methane derivative offormula CHR³ X'X" (wherein R³ is as defined above and X' and X" are,independently, a leaving group) has a moiety that can be represented asM'--CHR³ L (wherein M' is a metal, such as zinc or aluminium, R³ is asdefined above, and L is a leaving group). Such metallocarbons includezinc compounds which can be made, for example, by reacting a dialkylzinc of formula R¹¹ R¹² Zn (wherein R¹¹ and R¹² are, independently,unsubstituted alkyl) and which is, for example, diethyl zinc!, with amethane derivative of formula CHR³ X'X" (wherein X' and X" are,independently, a leaving group (such as a halogen (for example chlorine,bromine or iodine), a sulphurous acid (for example mesylate ortosylate), a carboxylate or a triflate) and which is, for example,ClCHR³ I (such as ClCH₂ I) or R³ CHI₂. These zinc compounds can berepresented as X'--ZnCHR³ X" (for example I--ZnCH₂ I. I--ZnCH₂ Cl orI--Zn--CHR³ I) Zn(CH₂ X')₂ or R¹¹ ZnCH₂ X'. Alternatively, suchmetallocarbons include aluminium compounds made, for example, byreacting a trialkyl aluminium of formula R¹¹ R¹² R¹⁷ Al (wherein R¹¹,R¹² and R¹⁷ are, independently, unsubstituted alkyl) with a methanederivative of formula CHR³ X'X", wherein R³, X' and X" are as definedabove. These aluminium compounds can be represented as R¹¹ R¹² Al(CH₂X').

All alkyl groups can be substituted by one or more of aryl (such asphenyl), cycloalkyl (such as cyclopropyl), C₁₋₆ alkoxy (such as methoxyor ethoxy), C₁₋₆ thioalkyl (such as methylthio), halogen (to form, forexample, CF₃ or CH₂ CF₃), C₁₋₆ haloalkoxy (such as OCF₃) or CO₂(C₁₋₆)alkyl. In addition the alkyl groups of R⁴ or R⁵ may terminate withan aldehyde (C(H)═O) group or be interrupted with a carbonyl (C═O)group.

All aryl and heteroaromatic groups can be substituted. The groups, whensubstituted, are preferably substituted by one or more of alkyl,haloalkyl, C₁₋₆ alkoxy, halogen, C₁₋₆ haloalkoxy, cycloalkyl, nitro,cyano or CO₂ (C₁₋₆)alkyl.

Cycloalkyl rings contain, preferably from 3 to 7, especially from 3 to 6carbon atoms. Cycloalkyl rings, can be substituted by one or more alkylgroups, CO₂ R⁸ (wherein R⁸ is as defined above) or two ring carbons maybe joined to each other by a carbon chain containing from 1 to 4(preferably 1 or 2) carbon atoms to form a bicyclic structure.

In one aspect the present invention provides a process for thepreparation of an oxirane, aziridine or cyclopropane of formula (I),wherein, X is oxygen, NR⁴ or CHR⁵ ; R¹ is hydrogen, alkyl, aryl,heteroaromatic, heterocyclic or cycloalkyl; R² is hydrogen, alkyl, aryl,heteroaromatic, CO₂ R⁸, heterocyclic or cycloalkyl; or R¹ and R² jointogether to form a cycloalkyl ring; R³ is hydrogen, alkyl, aryl,heteroaromatic, CO₂ R⁸, R⁸ ₃ Sn or trimethylsilyl; R⁴ and R⁵ are,independently, alkyl, cycloalkyl, aryl, heteroaromatic, SO₂ R⁸, SO₃ R⁸,CO₂ R⁸, CONR⁸ R⁹ ; R⁸ and R⁹ are independently alkyl or aryl; theprocess comprising reacting a mixture of a compound of formula (II),wherein R¹, R² and X are as defined above, and a sulphide of formula SR⁶R⁷, wherein R⁶ and R⁷ are independently alkyl, aryl or heteroaromatic,or R⁶ and R⁷ join together to form a cycloalkyl ring which optionallyincludes an additional heteroatom, with either (i) a metallocarbon offormula M'--CHR³ L, wherein L is a leaving group and M' is a metal, or(ii) a metallocarbon obtainable by reacting a compound of formula (III)(wherein R³ may not be hydrogen) with a suitable organometallic orinorganic reagent.

In another aspect the present invention provides a process for thepreparation of an oxirane, aziridine or cyclopropane of formula (I),wherein, X is oxygen, NR⁴ or CHR⁵ ; R¹ is hydrogen, alkyl, aryl,heteroaromatic, heterocyclic, NHR¹³ or cycloalkyl; R² is hydrogen,alkyl, aryl, heteroaromatic, CO₂ R⁸, CHR¹⁴ NHR¹³, heterocyclic orcycloalkyl; or R¹ and R² join together to form a cycloalkyl ring; R³ ishydrogen, alkyl, aryl, heteroaromatic, CO₂ R⁸, R⁸ ₃ Sn, CONR⁸ R⁹ ortrimethylsilyl; R⁴ and R⁵ are, independently, alkyl, cycloalkyl, aryl,heteroaromatic, SO₂ R⁸, SO₃ R⁸, CO₂ R⁸, CONR⁸ R⁹ or CN; R⁸ and R⁹ areindependently alkyl or aryl; R¹³ and R¹⁴ are independently hydrogen,alkyl or aryl; the process comprising reacting a mixture of a compoundof formula (II), wherein R¹, R² and X are as defined above, and asulphide of formula SR⁶ R⁷, wherein R⁶ and R⁷ are independently alkyl,aryl or heteroaromatic, or R⁶ and R⁷ join together to form a cycloalkylring which optionally includes an additional heteroatom, with either (i)a metallocarbon of formula M'--CHR³ L, wherein L is a leaving group andM' is a metal, or (ii) a metallcarbon obtainable by reacting a compoundof formula (III) (wherein R³ may not be hydrogen) with a suitableorganometallic or inorganic reagent.

In a further aspect the present invention provides a process as definedabove wherein R¹ is hydrogen.

In a still further aspect the present invention provides a processcomprising the steps:

a) reacting a metallocarbon (obtainable by reacting an alkyl metal witha methane derivative of formula CHR³ X'X") with a sulphide of formulaSR⁶ R⁷ ; and

b) reacting the product of (a) with a compound of formula (II).

In another aspect the present invention provides a process comprisingthe steps:

a) reacting an alkyl metal with a methane derivative of formula CHR³X'X";

b) reacting the product of (a) with a sulphide of formula SR⁶ R⁷ ; and

c) reacting the product of (b) with a compound of formula (II).

In a further aspect the present invention provides a process comprisingthe steps:

a) reacting a metallocarbon (obtainable by reacting a compound offormula (III) (wherein R³ is not hydrogen) with a suitableorganometallic or inorganic reagent) with a sulphide of formula SR⁶ R⁷ ;and,

b) reacting the product of (a) with a compound of formula (II).

In a still further aspect the present invention provides a processcomprising the steps:

a) reacting a compound of formula (III) (wherein R³ is not hydrogen)with a suitable organometallic or inorganic reagent;

b) reacting the product of (a) with a sulphide of formula SR⁶ R⁷ ; and,

c) reacting the product of (b) with a compound of formula (II).

In a further aspect the present invention provides a process forpreparing a compound of formula (I) wherein the metallocarbon species isobtainable by reacting a compound of formula (III) (wherein R³ is alkyl,aryl, heteroaromatic, CO₂ R⁸, R⁸ ₃ Sn, CONR⁸ R⁹ or trimethylsilyl) witha suitable organometallic or inorganic reagent.

For the process (ii) it is preferred that the nucleophilicity of thesulphide of formula SR⁶ R⁷ is such that the rate of reaction of themetallocarbon with the sulphide of formula SR⁶ R⁷ is greater than therate of reaction of the metallocarbon with the compound of formula(III).

In another aspect the present invention provides a process for preparinga compound of formula (I), wherein X, R¹, R², R³, R⁴ and R⁵ are asdefined above, the process comprising adding a compound of formula(III), wherein R³ is as defined above, to a mixture of a sulphide offormula SR⁶ R⁷, wherein R⁶ and R⁷ are as defined above, a compound offormula (II), wherein R¹, R² and X are as defined above, and anorganometallic or inorganic reagent.

In a further aspect the present invention provides a process forpreparing a compound of formula (I), wherein X, R¹, R², R³, R⁴ and R⁵are as defined above, the process comprising adding a mixture of acompound of formula (III), wherein R³ is as defined above, and asulphide of formula SR⁶ R⁷, wherein R⁶ and R⁷ are as defined above, to amixture of a compound of formula (II), wherein R¹, R² and X are asdefined above, and an organometallic or inorganic reagent.

It is possible to influence the stereochemistry of the compound offormula (I) produced by the process. This can be done by using a chiralsulphide of formula SR⁶ R⁷ (such as formulae (B) to (F)). The relativeamounts of the stereochemical products will depend on the nature of thechiral sulphide used.

In another aspect the present invention provides the process (ii) aspreviously described wherein the organometallic reagent is present in aless than stoichiometric amount (such as from 0.5 to 0.001, for examplefrom 0.015 to 0.005, equivalents).

In a further aspect the present invention provides the process (ii) aspreviously described wherein a solution of the compound of formula (III)(wherein R³ is as defined above but is not hydrogen) is added slowly(for example over a period of 2-36, especially 5-24, hours) to asolution of a sulphide of formula SR⁶ R⁷, a compound of formula (II) andan organometallic or inorganic reagent. By adding slowly a lowconcentration of the compound of formula (III) is maintained and theyield of the compound of formula (I) is increased. Under theseconditions it is possible to use a less than a stoichiometric amount ofsulphide (such as from 0.75 to 0.01, preferably from 0.75 to 0.1, forexample from 0.5 to 0.1 (such as 0.2), equivalents).

In a still further aspect the present invention provides a process ashereinbefore described wherein the compound of formula (II) is analdehyde, imine or alkene.

In another aspect the present invention provides a process as definedabove wherein X is oxygen.

Where it is used, it is preferred that the compound of formula (III) ispurified (for example by distillation) before being used in the processof the invention.

In a still further aspect the present invention provides a process forthe preparation of a compound of formula (I) wherein X is as definedabove (but is preferably oxygen) and R¹, R² and R³ are as defined above(but R³ is not hydrogen), the process comprising adding a compound offormula (III), wherein R³ is as defined above (but not hydrogen), to amixture of a compound of formula (II), wherein R¹ and R² are as definedabove and X is oxygen, a sulphide of formula SR⁶ R⁷, wherein R⁶ and R⁷are as defined above, a compound of formula (II), wherein R¹ and R² areas defined above and X is oxygen, and a rhodium compound of formula Rh₂(OCOR*)₄, wherein R* is as defined above (but is preferably methyl), themixture being in the presence of a solvent. It is believed that thisprocess proceeds as shown in Scheme 1.

In another aspect the present invention provides a process for thepreparation of a compound of formula (I) wherein X is as defined above(preferably oxygen), and R¹, R² and R³ are as defined above (R³ isespecially hydrogen) the process comprising adding a compound of formulaCHR³ X'X" to a compound of formula R¹¹ R¹² Zn preferably in a suitablesolvent preferably at a temperature in the range -50° to 10° C. (such as-30° to 0° C.) to form a metallocarbon that can be represented asZn--CHR³ X'!, then adding a sulphide of formula SR⁶ R⁷, and then addinga compound of formula (II) preferably at a temperature in the range 0°to 60° C. It is preferred that the compound of formula (II) is addedsome time after (for example 5-90, especially 10-60, minutes after) thesulphide of formula SR⁶ R⁷ is added. It is believed that this processproceeds as shown in Scheme 2 It is preferred that this process iscarried out under anhydrous conditions.

The following Examples illustrate the invention. The followingabbreviations are used throughout the Examples:

m.p.=melting point

b.p.=boiling point

Ac=acetate

m=multiplet

s=singlet

d=doublet

dd=doublet of doublets

ddd=doublet of doublet of doublets

t=triplet

dt=doublet of triplets

ppm=parts per million

petrol=petroleum ether boiling in the range 60°-80° C.

Lit.¹ =C. G. Overberger et al J. Org. Chem. (1963) 28 592

Phenyl diazomethane can be prepared as described below or,alternatively, using the method described in Organic Synthesis 64 207.Where necessary, apparatus, reagents or solvents were dried before use.

EXAMPLE 1 N-Benzyl-p-toluene sulphonamide

To a solution of benzylamine (5 g, 4.67 mmol) in pyridine (25 ml) wasadded (cautiously) p-toluenesulphonyl chloride (10 g, 5.25 mmol). Thedeep red coloured solution was stirred at room temperature for 1 hourbefore being poured into water (80-100 ml). The oily precipitate whichsolidified on scratching was filtered and recrystallised from ethanol togive the title compound (10.98 g, 90% yield, m.p. 115°-116° C., (Lit.¹114° C.)). δ_(H) (CDCl₃): 7.80(2H,m); 7.25(7H,m); 4.95(1H,t);4.05(2H,d); 2.35(3H,s)ppm.

N-Nitroso-N-benzyl-p-toluenesulphonamide

To a solution of N-benzyl-p-toluenesulphonamide (21 g, 80 mmol) andacetic acid (100 ml) in acetic anhydride (400 ml) was added solid sodiumnitrite (120 g, 1.7 mol) in portions over a period of 12 hours at 5° C.The temperature was kept below 10° C. all the time. After the additionwas finished the reaction mixture was stirred at room temperature for 18hours. The reaction mixture was poured over an excess of ice water andstirred for 1 hour. The pale yellow precipitate was filtered and washedseveral times with water. The crude product was recrystallized fromethanol to give the title compound as a tiny yellow needles (19.1 g, 82%yield, m.p. 92°-93° C., (Lit.¹ 89°-90° C.). δ_(H) (CDCl₃): 7.80(2H,m);7.25(7H,m); 4.95(2H,s); 2.40(3H,s)ppm.

Phenyldiazomethane (solution in tert-butyl methyl ether)

To a solution of sodium methoxide (1.2 equivalent, 4.0 ml of 1M solutionin methanol) in tert-butyl methyl ether (12 ml) was addedN-nitroso-N-benzyl-p-toluenesulphonamide (966 mg, 3.34 mmol) in smallportions at room temperature. After the addition was finished thereaction mixture was refluxed for 15-30 minutes. The reaction mixturewas cooled and washed with water (3×12 ml). The etheral solution ofphenyldiazomethane was dried over sodium sulphate for 30 minutes.

Decomposition of Phenyldiazomethane With Rh₂ (OCOCH₃)₄ In the Presenceof Dimethylsulphide and an Aldehyde

The following general procedure was used for Examples 2-6. To a stirredsolution of dimethylsulphide (0.5 mmol), rhodium (II) acetate (0.01mmol) and the aldehyde (1 mmol) in dichloromethane (4 ml) was added asolution of phenyldiazomethane (2 mmol in 6 ml of tert-butyl methylether) at room temperature over a period of 24 hours. After the additionwas completed the solvent was removed in vacuo and the residue waschromatographed over silica eluent dichloromethane:petrol (2:3)!.

EXAMPLE 2 Trans-Stilbene oxide

Following the procedure described in Example 1 and using benzaldehyde asthe aldehyde, the title oxirane was obtained in 70% yield. δ_(H)(CDCl₃): 7.35(10H,m); 3.85(2H,s)ppm.

EXAMPLE 3 Trans-2-(4-Nitrophenyl)-3-phenyloxirane

Following the procedure described in Example 1 and using4-nitrobenzaldehyde as the aldehyde, the title oxirane was obtained in79% yield. δ_(H) (CDCl₃): 8.30(2H,m); 7.30(7H,m); 3.95(1H,d);3.85(1H,d)ppm.

EXAMPLE 4 2-Cyclohexyl-3-phenyloxirane

Following the procedure described in Example 1 and usingcyclohexanecarboxaldehyde as the aldehyde, the title oxirane wasobtained in 64% yield. The product was found to be a mixture of cis andtrans (21:79) isomers. δ_(H) (CDCl₃): 7.20(5H,m); 4.10(1H,d) (cisisomer); 3.70(1H,d) (trans isomer); 2.85 (1H,d) (cis isomer); 2.75(1H,d)(trans isomer); 2.0-0.90 (11H,m)ppm. δ_(C) (CDCl₃): 138.18, 135.18(C),128.42, 127.87, 127.91, 127.35, 126.33, 125.50, 67.43, 63.92, 57.46,40.53, 34.92 (CH), 30.33, 29.62, 29.02, 28.10, 26.29, 25.20, 25.71,25.56, 25.27, 25.20 (CH₂).

EXAMPLE 5 2-n-Butyl-3-phenyloxirane

Following the procedure described in Example 1 and using valeraldehydeas the aldehyde, the title oxirane was obtained in 59% yield. Theproduct was found to be a mixture of cis and trans (44:56) isomers.δ_(H) (CDCl₃): 7.35(5H,m); 4.0(1H,d) (cis isomer); 3.55(1H,d) (transisomer); 3.15(1H,d) (cis isomer); 2.85(1H,d) (trans isomer);1.90-0.90(7H,m)ppm. δ_(C) (CDCl₃): 137.98, 135.82 (C), 128.58, 128.44,127.98, 127.43, 126.49, 125.53, 63.12, 62.85, 59.57, 58.64, 57.46 (CH),32.08, 28.18, 28.02, 22.55 (CH₂) 14.02, 13.89 (CH₃).

EXAMPLE 6 2-(1-Methylethyl)-3-phenyloxirane

Following the procedure described in Example 1 and usingiso-butyraldehyde as the aldehyde, the title oxirane was obtained in 55%yield. The product was found to be a mixture of cis and trans (40:60)isomers. δ_(H) (CDCl₃): 7.35(5H,m); 4.05(1H,d) (cis isomer); 3.60(1H,d)(trans isomer); 2.85(1H,d) (cis isomer); 2.70(1H,d) (trans isomer);1.64(1H,dd); 1.02(3H,d); 0.90(3H,d). δ_(C) (CDCl₃): 138.05, 135.85 (C),128.43, 127.97, 127.38, 126.32, 125.52, 68.36, 65.18, 57.79, 57.65,30.98, 25.87 (CH), 19.91, 19.04, 18.43, 17.91 (CH₃).

EXAMPLE 7 2-(4-Chlorophenyl)-3-phenyloxirane

To a stirred solution of a sulphide of formula (B), wherein R' ishydrogen, (0.5 mmol), rhodium (II) acetate (0.01 mmol) and4-chlorobenzaldehyde (1 mmol) in dichloromethane (4 ml) was added asolution of phenyldiazomethane (1 mmol in 6 ml of tert-butylmethylether, as prepared in Example 1) at room temperature over a period of 24hours. After addition was completed the solvent was removed in vacuo andthe residue was chromatographed over silica (eluentdichloromethane:petrol, 2:3) to give the trans oxirane (160 mg, 70%yield and 11% ee) and the cis oxirane (30 mg, 16% yield).

EXAMPLE 8 Stilbene oxide

Following the procedure described in Example 7, but using benzaldehydein place of p-chlorobenzaldehyde, trans stilbene oxide (117 mg, 61%yield and 11% ee) and cis stilbene oxide (23 mg, 10% yield) wereobtained.

EXAMPLE 9 Trans-Stilbene oxide

To a stirred solution of tetrahydrothiophene (0.5 mmol), rhodium (II)acetate (0.01 mmol) and benzaldehyde (1 mmol) in dichloromethane (4 ml)was added a solution of phenyldiazomethane (1 mmol in 6 ml oftert-butylmethyl ether, as prepared in Example 1) at room temperatureover a period of 24 hours. After addition was completed the solvent wasremoved in vacuo and the residue was chromatographed over silica (eluentdichloromethane:petrol, 2:3) to give the trans epoxide in 76% yield.

EXAMPLE 10 Trans-2-(4-Nitrophenyl)-3-phenyloxirane

Following the procedure described in Example 9, but using4-nitrobenzaldehyde in place of benzaldehyde, the title oxirane wasobtained in 78% yield.

EXAMPLE 11 2-(1-Methylethyl)-3-phenyloxirane

Following the procedure described in Example 9, but usingiso-butyraldehyde in place of benzaldehyde, the title oxirane wasobtained in 60% yield. The product was found to be a 55:45 mixture oftrans:cis isomers.

EXAMPLE 12 2-Cyclohexyl-3-phenyloxirane

Following the procedure described in Example 9, but usingcyclohexanecarboxaldehyde in place of benzaldehyde, the title oxiranewas obtained in 72% yield. The product was found to be a 80:20 mixtureof trans:cis isomers.

EXAMPLE 13 2-n-Butyl-3-phenyloxirane

Following the procedure described in Example 9, but using valeraldehydein place of benzaldehyde, the title oxirane was obtained in 64% yield.The product was found to be a 52:48 mixture of trans:cis isomers.

EXAMPLE 14 Trans-2-Methyl-2-(4-nitrophenyl)-3-phenyloxirane

To a stirred solution of dimethylsulphide (73 μl, 1 mmol), rhodium (II)acetate (4.0 mg, 0.01 mmol) and p-nitroacetophenone (140 mg, 1 mmol) indichloromethane (4 ml) was added a solution of phenyldiazomethane (1mmol in 6 ml of tert-butylmethyl ether, as prepared in Example 1) atroom temperature over a period of 24 hours. After addition was completedthe solvent was removed in vacuo and the residue was chromatographedover silica (eluent dichloromethane:petrol, 2:3) to give the transepoxide (143 mg, 56% yield) as a white solid m.p. 93°-94° C. δ_(H)(CDCl₃): 8.01(2H,m); 7.4(2H,m); 7.01(5H,m); 4.25(1H,s); 1.8(3H,s) ppm.

EXAMPLE 15 2-(Ethyl cycloprop-1-yl-2-carboxylate)-3-phenyloxirane

Using ethyl 2-formyl-1-cyclopropanecarboxylate, the title epoxide wasobtained in 72% yield following the same procedure described in Example9. The product was found to be a 50:50 mixture of cis:trans isomers onthe epoxide ring. δ_(H) (CDCl₃): 7.25(5H,m); 3.75(1H,d); 3.6(1H,d);2.95(1H,dd); 2.8(1H,dd); 1.75(2H,m); 1.25(5H,m) ppm.

EXAMPLE 16 Phenyldiazomethane (solution in diethyl ether)

To a solution of sodium methoxide (600 μl of 1M solution in methanol) indiethyl ether (6 ml) was added N-nitroso-N-benzyl-p-toluenesulphonamide(483 mg, 1.67 mmol, prepared as in Example 1), in small portions at roomtemperature. After the addition was finished the reaction mixture wasrefluxed for 15-30 minutes. The reaction mixture was cooled and washedwith water (3×6 ml). The etheral solution of phenyldiazomethane (1 mmol)was dried over sodium sulphate for 30 minutes.

Decomposition of Phenyldiazomethane With Rh₂ (OCOCH₃)₄ In the Presenceof Dimethylsulphide and an Aldehyde

The following general procedure was used for Examples 17-21. To astirred solution of dimethylsulphide (1 mmol), rhodium (II) acetate(0.01 mmol) and the aldehyde (1 mmol) in dichloromethane (4 ml) wasadded a solution of phenyldiazomethane (1 mmol in 6 ml of diethyl ether)at room temperature over a period of 3 hours. After the addition wascompleted the solvent was removed in vacuo and the residue waschromatographed over silica eluent dichloromethane:petrol (2:3)!.

EXAMPLE 17 Trans-Stilbene oxide

Following the procedure described in Example 16 and using benzaldehydeas the aldehyde, the title oxirane was obtained in 70% yield.

EXAMPLE 18 Trans-2-(4-Nitrophenyl)-3-phenyloxirane

Following the procedure described in Example 16 and using4-nitrobenzaldehyde as the aldehyde, the title oxirane was obtained in62% yield.

EXAMPLE 19 2-Cyclohexyl-3-phenyloxirane

Following the procedure described in Example 16 and usingcyclohexanecarboxaldehyde as the aldehyde, the title oxirane wasobtained in 66% yield. The product was found to be a mixture of cis andtrans (21:79) isomers.

EXAMPLE 20 2-n-Butyl-3-phenyloxirane

Following the procedure described in Example 16 and using valeraldehydeas the aldehyde, the title oxirane was obtained in 55% yield. Theproduct was found to be a mixture of cis and trans (44:56) isomers.

EXAMPLE 21 2-(1-Methylethyl)-3-phenyloxirane

Following the procedure described in Example 16 and usingiso-butyraldehyde as the aldehyde, the title oxirane was obtained in 64%yield. The product was found to be a mixture of cis and trans (40:60)isomers.

EXAMPLE 22 Ethyl (3-phenyloxiran-2-yl)cycloprop-2-yl)carboxylate

Following the procedure described in Example 9, but using ethyl2-formyl-1-cyclopropanecarboxylate in place of benzaldehyde, the titleoxirane was obtained in 72% yield. The product was found to be a 50:50mixture of trans:cis isomers. δ_(H) (CDCl₃): 7.25(5H,m); 3.75(1H,d,J=2Hz) (cis isomer); 3.6(1H,d,J=2 Hz)(trans isomer); 2.95(1H,dd,J=2Hz,J=3.5 Hz) (cis isomer); 2.8(1H,dd,J=2.0 Hz,J=4.5 Hz) (trans isomer);1.75 (m,2H); 1.25(5H,m)ppm.

EXAMPLE 23 2-(4-Acetyloxyphenyl)-3-phenyloxirane

Following the procedure described in Example 9, but using4-acetoxybenzaldehyde in place of benzaldehyde, the title oxirane wasobtained in 20% yield. δ_(H) (CDCl₃): 7.10-7.45(9H,m); 3.85(1H,d,J=2Hz); 2.80(1H,d,J=2.0 Hz); 2.25(3H,s)ppm.

EXAMPLE 24 Styrene oxide

To a solution of diethyl zinc (1.8 ml of 1.1M solution in toluene, 2.0mmol) in 1,2-dichloroethane (6 ml) was added chloroiododomethane (218μl. 3 mmol) at -15° C. and the reaction mixture was stirred for 15minutes. Tetrahydrothiophene (240 μl , 3 mmol) and benzaldehyde (1 mmol)were added and the reaction mixture was warmed to room temperature.After stirring at that temperature for 1 hour the reaction mixture wasrefluxed for one hour. After cooling to room temperature, the reactionmixture was diluted with dichloromethane (20 ml) and washed withsaturated solution of NH₄ Cl (3×5 ml). The organic layer was dried overMgSO₄. After filtration of the drying agent the solvent was removed invacuo and the residue was chromatographed over silica (eluantpetrol:dichloromethane (40:60) to give the title compound as a clear oil(92%).

EXAMPLE 25 p-Nitrostyrene oxide

Following the procedure described in Example 24, but usingp-nitrobenzaldehyde, in place of benzaldehyde, the title oxirane wasproduced in 95% yield.

EXAMPLE 26 4-Chlorostyrene oxide

Following the procedure described in Example 24, but using4-chlorobenzaldehyde in place of benzaldehyde, the title oxirane wasproduced in 65% yield.

EXAMPLE 27 Cyclohexylethylene oxide

Following the procedure described in Example 24, but using cyclohexanecarboxaldehyde in place of benzaldehyde, the title oxirane was producedin 60% yield.

EXAMPLE 28 2-(4-Chlorophenyl)-3-phenyloxirane

To a stirred solution of tetrahydrothiophene (0.1 mmol), rhodium (II)acetate (0.01 mmol) and p-chlorobenzaldehyde (1 mmol) in dichloromethane(4 ml) was added a solution of phenyldiazomethane (1 mmol in 6 ml oftert-butylmethyl ether) at room temperature over a period of 24 hours.After addition was completed the solvent was removed in vacuo and theresidue was chromatographed over silica to provide the title oxirane in26% yield.

EXAMPLE 29 2-(4-Chlorophenyl)-3-phenyloxirane

To a stirred solution of dimethyl sulphide (0.1 mmol), rhodium (II)acetate (0.01 mmol) and p-chlorobenzaldehyde (1 mmol) in dichloromethane(4 ml) was added a solution of phenyldiazomethane (1 mmol in 6 ml oftert-butylmethyl ether) at room temperature over a period of 24 hours.After addition was completed the solvent was removed in vacuo and theresidue was chromatographed over silica to provide the title oxirane in46% yield.

EXAMPLE 30 2-(4-Chlorophenyl)-3-phenyloxirane

To a stirred solution of dimethyl sulphide (0.25 mmol), rhodium (II)acetate (0.01 mmol) and p-chlorobenzaldehyde (1 mmol) in dichloromethane(4 ml) was added a solution of phenyldiazomethane (1 mmol in 6 ml oftert-butylmethyl ether) at room temperature over a period of 24 hours.After addition was completed the solvent was removed in vacuo and theresidue was chromatographed over silica to provide the title oxirane in76% yield.

EXAMPLE 31 2-(4-Chlorophenyl)-3-phenyloxirane

To a stirred solution of dimethyl sulphide (0.20 mmol), rhodium (II)acetate (0.01 mmol) and p-chlorobenzaldehyde (1 mmol) in dichloromethane(4 ml) was added a solution of phenyldiazomethane (1 mmol in 6 ml oftert-butylmethyl ether) at room temperature over a period of 24 hours.After addition was completed the solvent was removed in vacuo and theresidue was chromatographed over silica to provide the title oxirane in76% yield.

EXAMPLE 32 Stilbene oxide

Following the procedure described in Example 31, but using benzaldehydein place of p-chlorobenzaldehyde, the title oxirane was produced in 74%yield.

EXAMPLE 33 2-Cyclohexyl-3-phenyloxirane

Following the procedure described in Example 31, but using cyclohexanecarboxaldehyde in place of p-chlorobenzeldehyde, the title oxirane wasproduced in 51% yield.

EXAMPLE 34 2-n-Butyl-3-phenyloxirane

Following the procedure described in Example 31, but using valeraldehydein place of p-chlorobenzeldehyde, the title oxirane was produced in 45%yield.

EXAMPLE 35 2-(4-Nitrophenyl)-3-phenyloxirane

Following the procedure described in Example 31, but usingp-nitrobenzaldehyde in place of p-chlorobenzeldehyde, the title oxiranewas produced in 89% yield.

EXAMPLE 36 Phenyl diazomethane

N-Nitroso-N-benzyl-p-toluene sulphonamide (966 mg, 3.33 mmol) was addedin small portions to a solution of sodium methoxide (2.0 ml of 2Msolution in methanol) in t-butyl methyl ether (12 ml) and methanol (2ml) at room temperature. After the addition was finished the reactionmixture was refluxed for 15-30 min. The reaction mixture was cooled andwashed with water (3×6 ml). The ethereal solution of phenyl diazomethanewas dried over sodium sulphate for 30 minutes. The solvent was removedin vacuo and the residue distilled under reduce pressure to give phenyldiazomethane as a dark red oil (30% yield, b.p. 20° C. at 1 mmHg) whichwas immediately dissolved in t-butyl methyl ether (6 ml).

General Method For Epoxidation Using Phenyldiazomethane, an Aldehyde andRh₂ (OAc)₄ in the Presence of Dimethyl Sulfide

Phenyl diazomethane (1 mmol in 6 ml of t-butyl methyl ether) was addedto a stirred solution of dimethyl sulfide (0.2 mmol), rhodium (II)acetate (4.0 mg, 0.01 mmol) and an aldehyde (1 mmol) in dichloromethane(4 ml) at room temperature over a period of 24 hours. After the additionwas complete the solvent was removed in vacuo and the residue waschromatographed using silica eluent dichloromethane:petrol (2:3)!.

EXAMPLE 37 Stilbene oxide

Using the method of Example 36 with benzaldehyde gave the title compoundin 74% yield as a mixture of cis and trans (12:88) isomers.

EXAMPLE 38 Trans-2-(4-Nitrophenyl)-3-phenyloxirane

Using the method of Example 36 with 4-nitrobenzaldehyde gave the titlecompound in 89% yield as a yellow solid m.p. 126°-128° C.

EXAMPLE 39 2-(4-Chlorophenyl)-3-phenyloxirane

Using the method of Example 36 with 4-chlorobenzaldehyde gave the titlecompound in 76% yield as a white solid and as a mixture of cis and trans(20:80) isomers.

EXAMPLE 40 2-Cyclohexyl-3-phenyloxirane

Using the method of Example 36 with cyclohexane carboxaldehyde gave thetitle compound in 51% yield as a clear oil and as a mixture of cis andtrans (21:79) isomers.

EXAMPLE 41 2-n-Butyl-3-phenyloxirane

Using the method of Example 36 with valeraldehyde gave the titlecompound in 45% yield as a clear oil and as a mixture of cis and trans(44:56) isomers.

EXAMPLE 42 2,2-Dimethyl-4-(3-phenyloxiran-2-yl)-1,3-dihydrodioxole

Using the method of Example 36 with2,2-dimethyl-4-formyl-1,3-dihydrodioxole but using 1 mmol of dimethylsulfide gave the title compound in 73% yield as a clear oil and as amixture of diastereomers. δ_(H) (CDCl₃, 400 MHz): 7.4-7.2(5H,m),4.3-3.90(4.4H,m), 3.87(0.33H,d,J=2.0 Hz 3.83(0.34H,d,J=2.0 Hz),3.62-3.56(0.33H, ddd,J=9.0 Hz,J=6.0 Hz,J=5.0 Hz), 3.30(0.33H,dd, J=4.0Hz, J=9.0 Hz), 3.15-3.10(0.67H,two dd, J=2.0 Hz, J=6.0 Hz), 1.30 and1.25 (6H,s) ppm.

EXAMPLE 43 Ethyl 2,3-epoxy-3-phenyl propionate

Using the method of Example 36 with ethyl glyoxylate but using 1 mmol ofdimethyl sulfide gave the title compound in 53% yield as a clear oil.δ_(H) (CDCl₃, 250 MHz): 7.4-7.2(5H,m), 4.36-4.20 (2H,m), 4.10(1H,d,J=2.0 Hz), 3.51 (1H,d,J=2.0 Hz), 1.50(3H,t,J=8 Hz)ppm.

EXAMPLE 44 1,3-Diphenyl-2,3-epoxypropane

Using the method of Example 36 with phenylacetaldehyde but using (1mmol) of dimethyl sulfide gave the title compound in 80% yield as aclear oil. δ_(H) (CDCl₃, 250 MHz): 7.3-7.1 (10H,m), 3.55 (1H,d,J=2.0Hz), 3.05 (1H, dt,J=6.0 Hz,J=2.0 Hz), 2.80 (2H,d,J=6.0 Hz)ppm.

EXAMPLE 45 Stilbene oxide

Phenyl diazomethane (1 mmol in 6 ml of t-butylmethylether) was added toa stirred solution of a sulphide of formula (B) wherein R' is hydrogen(0.2 mmol), rhodium (II) acetate (4.0 mg, 0.01 mmol) and benzaldehyde (1mmol) in dichloromethane (4 ml) at room temperature over a period of 24hours. After the addition was complete the solvent was removed in vacuoand the residue was chromatographed over silica eluentdichloromethane:petrol (2:3)! to give the titled compound in 58% yieldand 11% ee.

EXAMPLE 46 2-(4-Chlorophenyl)-3-phenyloxirane

Using the method of Example 45 with 4-chlorobenzaldehyde in place ofbenzaldehyde gave the title compound in 62% yield and 12% ee as a whitesolid. This was a mixture of cis and trans (16:84) isomers.

EXAMPLE 47 1-Benzoyl-2,3-diphenylcyclopropane

Phenyl diazomethane (prepared as in Example 36, 0.5 mmol in 3 ml oft-butyl methyl ether) was added to a stirred solution ofdimethylsulphide (7.3 ml; 0.1 mmol), rhodium (II) acetate (2 mg; 0.005mmol) and chalcone (103 mg; 0.5 mmol) in dichloromethane (2 ml) at roomtemperature over a period of 24 hours. After the addition was completethe solvent was removed in vacuo and the residue was chromatographedover silica eluent dichloromethane:petrol (2:3)!, to give the titlecompound as a 4:1 mixture of trans:cis cyclopropanes as a yellowy solid(58 mg; 39%).

δ_(H) (CDCl₃, 250 MHz); 3.27(0.8H,dd,J=6.5 and 9 Hz), 3.32(0.4H,d,J=5Hz), 3.38(0.8H,dd,J=5.5 and 9.5 Hz), 3.54(0.2H,t,J=5 Hz),3.62(0.8H,dd,J=5.5 and 6.5 Hz), 7-7.5(13H,m), 7.95(1.6H,m),8.15(0.4H,m)ppm.

The same method was applied for the cyclopropanation of chalcone using astoichiometric amount of dimethyl sulphide (36.5 μl; 0.5 mmol). Columnchromatography over silica afforded the title compound as a 5:1 mixtureof trans; cis cyclopropanes as a yellowy solid (54 mg; 36.2%.

EXAMPLE 48 Stilbene oxide

A solution of phenyldiazomethane (1 mmol in 6 ml of t-butyl methylether) was added, over a period of 12 hours, to a solution of a sulphideof formula (C) wherein R' and R" are both hydrogen (for preparation seeJ. Org. Chem. 44 (20) 3598-9 (1979); 198 mg, 1.0 mmol), rhodium (II)acetate (4 mg, 0.01 mmol) and benzaldehyde (190 μl, 1.0 mmol) indichloromethane (4 ml). Upon completion of the addition, the solvent wasremoved in vacuo and the residue chromatographed using silica geleluting with dichloromethane:petrol 40:60 to yield trans-2,3-diphenyloxirane (31 mg, 16%, 51%ee) and cis-2 3-diphenyl oxirane (3 mg, 1.5%).

EXAMPLE 49 Trans-Stilbene oxide

A mixture of boron trifluoroetherate (0.01 ml; 0.77 mmol) and glacialacetic acid (0.16 ml; 2.80 mmol) in minimum chloroform (2 ml) wasstirred and refluxed under nitrogen for 15 minutes. A mixture ofdimethoxymethane (0.07 ml; 0.79 mmol) and (+)-(10)-mercaptoborneol (0.13g; 0.70 mmol) in chloroform (3 ml) was then added slowly over 15minutes. The reaction mixture was refluxed for 30 minutes, before beingallowed to cool to room temperature. The reaction mixture was thenwashed with water (2×10 ml), brine solution (2×10 ml) and 10% aqueouspotassium hydroxide (2×10 ml). The organic fraction was dried overpotassium carbonate. The solvent was removed in vacuo, to yield a crudeproduct which was chromatographed eluting with 85:15 petrol:ethylacetate to produce a compound formula (C') wherein R' and R" are bothhydrogen (91 mg; 69%). ¹ H N.M.R. data: δ_(H) (CDCl₃) 4.58(1H,dd),4.67(1H,d), 3.41-3.48(1H,m), 2.67(1H,d), 2.30-2.42(1H,m), 2.28(1H,dd),1.91-2.13(1H,m), 1.38-1.62(2H,m), 0.96-1.22(2H,m), 0.72-0.90(1H,m),0.74(6H,s) ppm.

A solution of phenyldiazomethane (0.45 mmol in 6 ml of t-butylmethylether was added to a solution of a compound of formula (C') wherein R'and R" are both hydrogen (90 mg; 0.45 mmol), rhodium (II) acetate (2 mg;0.0045 mmol) and benzaldehyde (46 μl; 0.45 mmol) in dichloromethane (2ml). Upon completion of the addition, the solvent was removed in vacuoand the residue chromatographed using silica gel and elating withdichloromethane:petrol 40:60 to give the title compound (4 mg, 5%,71%ee).

EXAMPLE 50 2,3-Diphenyl-1-(4-methylphenylsulphonyl)aziridine

To a stirred solution of dimethylsulphide (7 μl, 0.1 mmol), rhodium (II)acetate (2 mg, 0.005 mmol) and N-benzylidene-toluene-p-sulphonamide (131mg, 0.5 mmol; J. C. S. Perkin I (1981) 2435-2442) in dichloromethane (2ml) was added phenyldiazomethane (prepared as in Example 36; 8.11 ml ofa 0.074M solution in t-butylmethylether) over a period of 12 hours. Uponcompletion of the addition, the solvent was removed in vacuo and theresidue chromatographed using silica gel eluting with 15:85 ethylacetate:petrol to give the title compound as a 3:1 mixture of trans:cisisomers (144 mg, 82%).

EXAMPLE 512-(4-Nitrophenyl)-3-phenyl-1-(4-methylphenylsulphonyl)aziridine

To a stirred solution of dimethylsulphide (5 μl, 0.07 mmol), rhodium(II) acetate (2 mg, 0.005 mmol) andN-(4-nitrobenzylidene)toluene-p-sulphonamide (102 mg, 0.33 mmol; J. C.S. Perkin I (1981) 2435-2442) in dichloromethane (2 ml) was addedphenyldiazomethane (prepared as in Example 36; 8.11 ml of a 0.074Msolution in t-butylmethylether) over a period of 12 hours. Uponcompletion of the addition the solvent was removed in vacuo and theresidue was chromatographed using silica gel elating with 15:85 ethylacetate:petrol to give the title compound as a mixture of trans and cisisomers. Trans isomer (48 mg, 37%) δ_(H) (CDCl₃) 8.10-8.19(2H,m),7.53-7.64(4H,m), 6.95-7.41(7H,m), 4.27(1H,d,J=6 Hz), 4.16(1H,d,J=6 Hz),2.36(3H,s)ppm. Cis isomer (9 mg; 7%) δ_(H) (CDCl₃) 8.23-8.33(2H,m);7.15-7.60(11H,m), 4.13(1H,d,J=2 Hz) 3.87(1H,d,J=2 Hz) 1.68(3H,s)ppm.

EXAMPLE 52Trans-2-(4-Methoxyphenyl)-3-phenyl-1-(4-methylphenylsulphonyl)aziridine

4-Methoxybenzaldehyde (1.22 ml, 10 mmol) and p-toluenesulphonamide (1.71g, 10 mmol) were refluxed in toluene (70 ml) for 5 minutes using a Deanand Stark apparatus. Reflux was maintained while BF₃ (C₂ H₅)₂ O (0.05ml, 0.4 mmol) was added via a syringe. The reaction mixture wasmaintained at reflux for 12 hours before being allowed to cool to roomtemperature whereby the title compound precipitated from the toluene.Filtration followed by recrystallisation from dichloromethane-petrolyielded N-(4-methoxybenzylidene)-toluene-p-sulphonamide as a yellowsolid (0.478 g; 17%) m.p. 127° C.

To a stirred solution of dimethylsulphide (7 μl, 0.1 mmol), rhodium (II)acetate (2 mg, 0.005 mmol) andN-(4-methoxybenzylidene)toluene-p-sulphonamide (144 mg, 0.5 mmol) indichloromethane (2 ml) was added phenyldiazomethane (prepared as inExample 36; 8.96 ml of a 0.067M solution in t-butylmethylether) over aperiod of 12 hours. Upon completion of the addition the solvent wasremoved in vacuo and the residue was chromatographed using silica geleluting with 15:85 ethyl acetate:petrol to give the title compound (96mg, 51%). δ_(H) (CDCl₃) 7.62(2H), 6.75-7.45(11H,m), 4.35(1H,d,J=6 Hz),4.18(1H,d,J=6 Hz), 3.62(3H,s), 2.35(3H,s)ppm.

EXAMPLE 53Trans-2-(N,N-Diethylacetamido)-3-phenyl-1-(4-methylphenylsulphonyl)aziridine

To a stirred solution of dimethylsulphide (0.014 ml, 0.2 mmol), rhodium(II) acetate (4 mg, 0.01 mmol) and N-benzylidenetoluene-p-sulphonamide(260 mg, 1.0 mmol) in dichloromethane (2 ml) was added a solution ofN,N-diethyldiazoacetamide (prepared by using N,N-diethylacetoacetamidein place of t-butylacetoacetate in a preparation described in Org.Synth. Collective Volume V page 179; 141 mg, 1.0 mmol, in 6 mlt-butylmethyl ether) over a period of 24 hours via a syringe pump. Uponcompletion of the addition, the solvent was removed in vacuo to yieldthe title compound (56 mg; 15%). δ_(H) (CDCl₃) 7.10-7.91(9H,m),4.40(1H,d,J=4 Hz), 3.10-4.10(4H, m), 3.40(1H,d,J=4 Hz), 2.30(3H,s),1.15(6H,m) ppm.

EXAMPLE 54 Trans-2-(N,N-Diethylacetamido)-3-(4-chlorophenyl)oxirane

To a stirred solution of tetrahydrothiophene (6 μl, 0.1 mmol), rhodium(II) acetate (2 mg, 0.005 mmol) and p-chlorobenzaldehyde (71 mg, 0.5mmol) in dichloromethane (2 ml) was added a solution ofN,N-diethyldiazoacetamide (see Example 53 for praparation, 70 mg, 0.5mmol, in 6 ml t-butylmethyl ether) over a period of 24 hours via asyringe pump at 60° C. Upon completion of the addition, the solvent wasremoved in vacuo and the residue chromatographed using silica geleluting with petrol:ethyl acetate 1:1 to yield the title compound (25mg, 20%). δ_(H) (CDCl₃) 1.14-1.30(6H,m), 3.30-3.52(4H,m), 3.53(1H,d,J=2Hz), 4.07(1H,d,J=2 Hz), 7.22-7.40(4H,m)ppm.

EXAMPLE 55 Styrene oxide

To a solution of diethyl zinc (18 ml of 1.1M solution in toluene, 20mmol) in 1,2-dichloroethane (60 ml) was added chloroiododomethane (2.18ml, 30 mmol) at -15° C. and the reaction mixture was stirred for 15minutes. Tetrahydrothiophene (2.40 ml, 30 mmol) was added at -15° C. andthe mixture was stirred for 25 minutes. During this time the temperaturewas allowed to rise to 19° C. Benzaldehyde (2.12 ml, 20 mmol) was addedand the reaction mixture was stirred until it reached room temperature.The reaction mixture was stirred at room temperature for 1 hour afterwhich it was diluted with dichloromethane (20 ml) and washed with asaturated solution of NH₄ Cl (3×5 ml). The organic layer was dried overMgSO₄. The resulting solution was analysed by gas chromatography and thetitle compound was found to be present.

EXAMPLE 56 2-Phenyl-3-vinyloxirane

To a stirred solution of dimethyl sulfide (1.0 mmol), rhodium (II)acetate (0.01 mmol) and acrolein (1 mmol) in dichloromethane (4 ml) wasadded a solution of phenyldiazomethane (1 mmol in 6 ml of tert-butylmethyl ether, prepared as in Example 1) at room temperature over aperiod of 3 hours. After the addition was completed the solvent wasremoved in vacuo and the residue was chromatographed over silica (eluantdichloromethanre:petrol; 40:60) to give the title compound in 54% yield.δ_(H) (CDCl₃); 7.20(5H,m), 5.75(1H,m), 5.5(1H,dd,J=2,J=12 Hz),4.85(1H,dd,J=2,J=12 Hz), 3.55(1H,d,J=2 Hz), 3.30(1H,dd,J=2,J=9 Hz)ppm.

EXAMPLE 57 2,3-Diphenyl-1-diphenylphosphinylaziridine

Diphenylphosphinic acid (10.0 g, 45.9 mmol) was heated gently at refluxin dry tolune (75 ml) with freshly distilled thionyl chloride (6.70 ml;91.8 mmol) for two hours, according to the method of Jennings (Jennings,W. B; Lovely, C. J; Tetrahedron, (1991) 47 5561). The solvent was thenremoved in vacuo to give crude diphenyl-N-phenylmethylene phosphinicchloride (9.0 g; 83%) which was used without further purification.

P,P-diphenylphosphinic amide was prepared following the method ofJennings (ibid) by adding crude diphenyl-N-phenylmethylene phosphinicchloride (9.0 g; 38.05 mmol, prepared above) in dry dichloromethane (20ml) to a stirred mixture of saturated ethanolic ammonia solution (100ml) and dry dichloromethane (40 ml) cooled using an ice/salt bath.Subsequent work-up gave P,P-diphenylphosphinic amide (7.2 g; 87%).

P,P-diphenyl-N-phenylmethylene phosphinic amide was prepared followingthe method of Jennings (ibid) by adding titanium tetrachloride (635 ml;5.78 mmol) in dry dichloromethane (10 ml) to a stirred solution ofbenzaldehyde (1.17 ml; 11.59 mmol), P,P-diphenylphosphinic amide (2.52g; 11.59 mmol) and anhydrous triethylamine (4.84 ml; 34.78 mmol) in drydichloromethane (50 ml) at 0° C. Upon completion of the addition, thestirring was maintained at 0° C. for a further 4 hours. Subsequentwork-up gave P,P-diphenyl-N-phenylmethylene phosphinic amide (1.4 g;40%).

To a sitrred solutuion of dimethyl sulfide (12 μl, 0.16 mmol), rhodium(II) acetate (3.5 mg; 0.0079 mmol) and P,P-diphenyl-N-phenylmethylenephosphinic amide (241 mg; 0.79 mmol) in dichloromethane (2 ml), wasadded a solution of phenyldiazomethane (8.4 ml of 0.094M solution intert-butyl methyl ether), at room temperature over 14 hours via asyringe pump. Upon completion of the addition, the solvent was removedin vacuo. Chromatography using 1:1 ethyl acetate:petrol gave a mixture(6:1) of trans- and cis- 2,3-diphenyl-1-diphenylphosphinyl aziridine(205 mg, 66%). δ_(H) (CDCl₃): 4.05(1.72H,d, J=16 Hz), 4.16(0.28H,d,J=18Hz), 7.10-7.45(16H,m), 7.50-7.65(1.72H,m), 7.75-7.85(1.72H,m),7.90-8.05(0.56H,m)ppm.

EXAMPLE 58 2-(3-Chlorophenyl)-3-phenyl oxirane

To a mixture of sodium methoxide solution (30% in methanol, 0.360 g),methanol (1.33 g) and tert-butylmethylether (5 ml) was addedN-nitroso-N-(3-chlorobenzyl)-p-toluenesulphonamide (0.54 g) over 15minutes. The resulting mixture was stirred at room temperature for 30minutes and then refluxed for 15 minutes. Water (4 ml) was added to themixture once it had cooled to room temperature. The organic layer waswashed with further quantities of water (2×4 ml) and then dried overanhydrous sodium sulphate. After decanting the organic solution from thesodium sulphate, the sodium sulphate was washed withtert-butylmethylether (2×1 ml) and these washings were combined with thedecanted organic solution of 3-chlorophenyldiazomethane.

To a slurry of rhodium (II) acetate (0.001 g) and dichloromethane (4 ml)were added benzaldehyde (0.025 ml) and dimethylsulphide (0.009 ml). Thesolution of 3-chlorophenyldiazomethane (produced above) was added tothis mixture over 24 hours. The solvent was removed in vacuo and theresidue chromatographed on silica (Merck grade 60, 230-400 mesh) elutingwith dichloromethane:hexane 2:3 to give the title compound as acolourless oil (0.0305 g, 53% yield) δ_(H) (CDCl₃): 7.55(8H); 7.45(1H),4.0(2H)ppm.

EXAMPLE 59 Stilbene oxide

To a mixture of rhodium (II) acetate (0.0021 g), dichloromethane (4 ml)and benzaldehyde (0.051 ml) was added 1-methoxy-4-methylthiobenzene(0.0036 ml). To this mixture was added, with stirring, a solution ofphenyldiazomethane (1 mmol in tert-butylmethyl ether (8 ml)) over 19hours. The reaction mixture was stirred or a further 5 hours after whichthe mixture was allowed to stand at room temperature for 2 days. Thesolvent was removed in vacuo and the residue chromatographed on silicausing dichloromethane:hexane 2:3 as eluant. The title compound wasobtained as a colourless oil (0.0713 g, 22.6% yield).

EXAMPLE 60 2-(4-Chlorophenyl)-3-phenyloxirane

Phenyldiazomethane (1 mmol in 6 ml of tert-butyl methyl ether, asprepared in Example 1), was added to a stirred solution ofdimethylsulphide (1.0 mmol), rhodium (II) trifluoroacetamide (0.01 mmol)and p-chlorobenzaldehyde (1 mmol) in dichloromethane (4 ml) at roomtemperature over a period of 3 hours. After the addition was completedthe solvent was removed in vacuo and the residue was chromatographedover silica (eluent dichloromethane:petrol (2:3)! to give the titlecompound in 83% yield. ##STR1##

We claim:
 1. A process for the preparation of an oxirane, aziridine orcyclopropane of formula (I):wherein, X is oxygen, NR⁴ or CHR⁵ ; R¹ ishydrogen, alkyl, aryl, heteroaromatic, heterocyclic or cycloalkyl; R² ishydrogen, alkyl, aryl, heteroaromatic, CO₂ R⁸, CHR¹⁴ NHR¹³, heterocyclicor cycloalkyl; or R¹ and R² join together to form a cycloalkyl ring; R³is hydrogen, alkyl, aryl, heteroaromatic, CO₂ R⁸, R⁸ ₃ Sn, CONR⁸ R⁹ ortrimethylsilyl; R⁴ and R⁵ are, independently, alkyl, cycloalkyl, aryl,heteroaromatic, SO₂ R⁸, SO₃ R⁸, COR⁸, CO₂ R⁸, CONR⁸ R⁹ or CN, or R⁴ canalso be P(O)(aryl)₂ ; R⁸ and R⁹ are independently alkyl, aryl orarylalkyl; R¹³ and R¹⁴ are independently hydrogen, alkyl or aryl; theprocess comprising: a) reacting a metallocarbon with a sulphide offormula SR⁶ R⁷, wherein R⁶ and R⁷ are independently alkyl, aryl orheteroaromatic, or R⁶ and R⁷ join together to form a cycloalkyl ringwhich optionally includes an additional heteroatom; and, b) reacting theproduct of step (a) with a compound of formula (II): ##STR2## whereinR¹, R² and X are as defined above.
 2. A process as claimed in claim 1wherein R¹ is hydrogen.
 3. A process as claimed in claim 1,comprising:a) reacting an alkyl metal with a methane derivative offormula CHR³ X'X"; b) reacting the product of (a) with a sulphide offormula SR⁶ R⁷ ; and c) reacting the product of (b) with a compound offormula (II).
 4. A process as claimed in claim 1, comprising:a) reactinga compound of formula (III) (wherein R³ is not hydrogen) with a suitableorganometallic or inorganic reagent; b) reacting the product of (a) witha sulphide of formula SR⁶ R⁷ ; and, c) reacting the product of (b) witha compound of formula (II).
 5. A process as claimed in claim 1,comprising adding a compound of formula (III) (wherein R³ is as definedin claim 1 but is not hydrogen) to a mixture of a sulphide of formulaSR⁶ R⁷, a compound of formula (II) and an organometallic or inorganicreagent.
 6. A process as claimed in claim 5 wherein the addition is overa period of 2 to 36 hours.
 7. A process as claimed in claim 5 or 6wherein the sulphide is present in a less than stoichiometric amount. 8.A process as claimed in claim 1 wherein the metallocarbon is prepared byreacting an alkylmetal with a methane derivative of formula CHR³ X'X",wherein R³ is as defined above, and X' and X" are independently, aleaving group.
 9. A process as claimed in claim 1 wherein themetallocarbon is prepared by reacting a compound of formula (III):##STR3## wherein R³ is as defined in claim 1 but is not hydrogen, with asuitable organometallic or inorganic reagent.
 10. A process as claimedin claim 9 wherein the suitable organometallic or inorganic reagent isrhodium (II) acetate or copper acetylacetonate.
 11. A process as claimedin claim 1 wherein the sulphide of formula SR⁶ R⁷ is a compound offormula (C): ##STR4## wherein R' is hydrogen, C₁₋₁₀ alkyl, phenyl orphenyl(C₁₋₆)alkyl; wherein the alkyl groups are optionally substitutedby phenyl, C₃₋₇ cycloalkyl, C₁₋₆ alkoxy, halogen, C₁₋₆ haloalkoxy or CO₂(C₁₋₆)alkyl; and wherein the phenyl groups are optionally substituted byone or more of halogen, C₁₋₁₀ alkyl, C₁₋₁₀ haloalkyl, C₁₋₆ alkoxy, C₁₋₆haloalkoxy, C₃₋₇ cycloalkyl, nitro, cyano or CO₂ (C₁₋₆)alkyl; and R" ishydrogen.